Placebo Controlled Trial of Bosentan in Scleroderma Patients

NCT00377455 | Terminated Phase 2 Results

• 2 other identifiers: IRB 06-043Bosentan
• Study Type: interventional
• Target: 5
• Locations: 1 country
• Sites: 2

Brief Summary

The purpose of this study is to determine whether the drug Bosentan improves exercise tolerance in scleroderma patients.

Conditions

Systemic Scleroderma; Pulmonary Hypertension

Keywords

scleroderma; systemic sclerosis; bosentan; pulmonary hypertension; PHAROS; PHROS; exercise echocardiogram

Outcome Measures

Primary Outcomes (1)

• Total Exercise Time on the Exercise Echocardiogram Using the Standard Bruce Stress Protocol.

  The total exercise time measured using the exercise echocardiogram is evaluated with the standard Bruce Stress Protocol, and this will be determined after 16 weeks on the study medication.

  This will be determined after 16 weeks on the study medication.

Secondary Outcomes (4)

• 6-minute Walk Distance

  16 weeks

• Brain Natriuretic Peptide (BNP) Level

  16 weeks

• Endothelin-1(ET-1) Level

  16 weeks

• Quality of Life (QOL)

  16 weeks

Study Arms (2)

Bosentan

EXPERIMENTAL

Drug: Bosentan

Placebo

PLACEBO COMPARATOR

Drug: Placebo

Interventions

Bosentan DRUG

62.5 mg by mouth (PO) twice daily (Bid) for 1 month, followed by 125 mg PO Bid thereafter, for a total of 16 weeks

Bosentan

Placebo DRUG

62.5 mg PO Bid for 1 month, followed by 125 mg PO Bid thereafter, for a total of 16 weeks

Placebo

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• SSc patients \> 18 with NYHA functional Class I/II symptoms, informed consent, and who are willing to participate in the Pulmonary Hypertension Assessment and Recognition of Outcomes in Scleroderma (PHAROS) long term study (Georgetown IRB 04-227)
• Right heart catheterization with
• Normal Mean Pulmonary Arterial Pressure (PAP) at rest
• Mean PAP \> 30 with exercise
• Wedge Pressure \< 18
• Entry criteria for participating in the exercise echocardiogram study (Georegtown IRB 03-363)
• Diffusing Capacity (DLCO) \<60 with a Forced Vital Capacity (FVC) \>60%, or
• FVC/DLCO \> 1.6, or
• a resting Pulmonary Arterial Systolic Pressure (PASP)\> 40mmHg

You may not qualify if:

• Established resting pulmonary hypertension
• Congestive heart failure
• Diastolic dysfunction
• Pregnancy
• Inability to adequately walk/exercise
• Severe liver disease

Sponsors & Collaborators

• Georgetown University: lead
• Actelion: collaborator

Study Sites (2)

University of Connecticut

Farmington, Connecticut, 06030, United States

Location

Georgetown University Medical Center

Washington D.C., District of Columbia, 20007, United States

Location

Related Publications (7)

• Stupi AM, Steen VD, Owens GR, Barnes EL, Rodnan GP, Medsger TA Jr. Pulmonary hypertension in the CREST syndrome variant of systemic sclerosis. Arthritis Rheum. 1986 Apr;29(4):515-24. doi: 10.1002/art.1780290409.

  PMID: 3707629 BACKGROUND

• Yousem SA. The pulmonary pathologic manifestations of the CREST syndrome. Hum Pathol. 1990 May;21(5):467-74. doi: 10.1016/0046-8177(90)90002-m.

  PMID: 2186993 BACKGROUND

• al-Sabbagh MR, Steen VD, Zee BC, Nalesnik M, Trostle DC, Bedetti CD, Medsger TA Jr. Pulmonary arterial histology and morphometry in systemic sclerosis: a case-control autopsy study. J Rheumatol. 1989 Aug;16(8):1038-42.

  PMID: 2585400 BACKGROUND

• MacGregor AJ, Canavan R, Knight C, Denton CP, Davar J, Coghlan J, Black CM. Pulmonary hypertension in systemic sclerosis: risk factors for progression and consequences for survival. Rheumatology (Oxford). 2001 Apr;40(4):453-9. doi: 10.1093/rheumatology/40.4.453.

  PMID: 11312386 BACKGROUND

• Grunig E, Janssen B, Mereles D, Barth U, Borst MM, Vogt IR, Fischer C, Olschewski H, Kuecherer HF, Kubler W. Abnormal pulmonary artery pressure response in asymptomatic carriers of primary pulmonary hypertension gene. Circulation. 2000 Sep 5;102(10):1145-50. doi: 10.1161/01.cir.102.10.1145.

  PMID: 10973844 BACKGROUND

• Steen V, Medsger TA Jr. Predictors of isolated pulmonary hypertension in patients with systemic sclerosis and limited cutaneous involvement. Arthritis Rheum. 2003 Feb;48(2):516-22. doi: 10.1002/art.10775.

  PMID: 12571862 BACKGROUND

• Rubin LJ, Badesch DB, Barst RJ, Galie N, Black CM, Keogh A, Pulido T, Frost A, Roux S, Leconte I, Landzberg M, Simonneau G. Bosentan therapy for pulmonary arterial hypertension. N Engl J Med. 2002 Mar 21;346(12):896-903. doi: 10.1056/NEJMoa012212.

  PMID: 11907289 BACKGROUND

MeSH Terms

Conditions

Scleroderma, Systemic; Hypertension, Pulmonary; Scleroderma, Diffuse

Interventions

Bosentan

Condition Hierarchy (Ancestors)

Connective Tissue Diseases; Skin and Connective Tissue Diseases; Skin Diseases; Lung Diseases; Respiratory Tract Diseases; Hypertension; Vascular Diseases; Cardiovascular Diseases

Intervention Hierarchy (Ancestors)

Benzenesulfonamides; Sulfonamides; Amides; Organic Chemicals; Benzene Derivatives; Hydrocarbons, Aromatic; Hydrocarbons, Cyclic; Hydrocarbons; Sulfones; Sulfur Compounds; Pyrimidines; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds

Results Point of Contact

• Title: Dr. Virginia Steen
• Organization: Georgetown University

steenv@georgetown.edu

202-444-6200

Study Officials

• Virginia D Steen, MD

  Georgetown University

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: Yes
• Restrictive Agreement: No

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Professor of Medicine

Study Record Dates

• First Submitted: September 14, 2006
• First Posted: September 18, 2006
• Study Start: September 1, 2006
• Primary Completion: September 1, 2009
• Study Completion: March 1, 2010
• Last Updated: May 24, 2018
• Results First Posted: July 20, 2011

Record last verified: 2018-04

Locations

US (2)